Proteins associated with the erythrocyte membrane appear to play a critical role in the determination of cell shape and deformability, i.e., survival. A detailed study of the membrane protein kinase system and its substrates will be undertaken in order to ascertain its importance in regulating shape and deformability of the cell. Particular attention will be paid to spectrin, its phosphorylation, and subsequent interaction with erythrocyte actin to form the cytoskeletal network of the membrane. The properties of spectrin, the phosphorylation reaction and spectrin-actin complex will be examined from normal and pathological red cells. By selectively modifying and inhibiting the membrane associated enzymes (protein kinases and adenosine triphosphatases), we hope to develop a coherent mechanism for the involvement of these proteins in controlling the erythrocyte shape and its deformability.